Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses

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38 Scopus citations


Observational research shows that higher body mass index (BMI) increases Alzheimer's disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian randomization analyses, an approach that is not biased by reverse causation or confounding, to evaluate whether higher BMI increases AD risk. We evaluated individual-level data from the AD Genetics Consortium (ADGC: 10,079 AD cases and 9613 controls), the Health and Retirement Study (HRS: 8403 participants with algorithm-predicted dementia status), and published associations from the Genetic and Environmental Risk for AD consortium (GERAD1: 3177 AD cases and 7277 controls). No evidence from individual single-nucleotide polymorphisms or polygenic scores indicated BMI increased AD risk. Mendelian randomization effect estimates per BMI point (95% confidence intervals) were as follows: ADGC, odds ratio (OR) = 0.95 (0.90-1.01); HRS, OR = 1.00 (0.75-1.32); GERAD1, OR = 0.96 (0.87-1.07). One subscore (cellular processes not otherwise specified) unexpectedly predicted lower AD risk.

Original languageEnglish
Pages (from-to)1439-1451
Number of pages13
JournalAlzheimer's and Dementia
Issue number12
StatePublished - Dec 1 2015

Bibliographical note

Funding Information:
ACT: ACT is supported by a grant ( U01 AG 06781 , to E.B.L. and P.K.C.) from the National Institutes of Health .

Funding Information:
ROS/MAP: ROS and MAP are supported by National Institute on Aging grants R01AG17917 , R01AG34374 , R01AG15819 , and P30AG10161 (all to D.A.B.).

Funding Information:
The Health and Retirement Study genetic data are sponsored by the National Institute on Aging (grant numbers U01AG009740 , RC2AG036495 , and RC4AG039029 ) and was conducted by the University of Michigan.

Publisher Copyright:
© 2015 The Alzheimer's Association.


  • Alzheimer's disease
  • Dementia
  • Mendelian randomization
  • Obesity

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health


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